tbuckley/cabot-search huggingface dataset:
Functional Titanium Substrates Synergetic Photothermal Therapy for Enhanced Antibacterial and Osteogenic Performance via Immunity Regulation
Authors: Kun Xu, Ke Li, Ye He, Xuan Li, Chuanchuan Lin, Jing Wu, Shaopeng Liu, Yao Ding, Yulu Yang, Shuangquan Gou, Peng Liu, Kaiyong Cai
Journal: Advanced Healthcare Materials (2023)

Abstract Implant‐associated infections (IAIs) significantly impair the integration between titanium (Ti) implants and bone tissues. Bacteria colonized on the surface of the implant can induce innate immune suppression of the host to resist clearance. Herein, an interfacial functionalization strategy is employed to introduce Fe III TA nanoparticles (NPs) and acetyl Bletilla striata polysaccharide (acBSP) on the Ti substrate to obtain the Ti‐TF‐acBSP system. Under near‐infrared (NIR) irradiation, the hyperthermal effect induced by Fe III TA NPs directly killed bacteria. Meanwhile, macrophages are induced by acBSP to polarize into pro‐inflammatory M1 phenotype, which enhanced the phagocytosis ability of macrophages and activated host innate immunity. Moreover, the asBSP instructed macrophages to secrete pro‐osteogenic cytokine, which promoted osteogenic differentiation of MSCs. The results of the animal experiment in vivo confirmed that the Ti‐TF‐acBSP implant effectively eliminated bacterial infection under NIR irradiation, enhanced the expression of pro‐inflammatory cytokine, and induced the production of bone‐forming related factors. In a word, the functionalized Ti implant not only have a direct bactericidal effect but also regulate macrophage polarization as well as macrophage‐mediated bactericidal and osteogenic effect. The strategy of combining photothermal therapy with immunoregulation will present a potential candidate for the development of novel antibacterial orthopedic devices.
Novel Genetic Subtypes of Urothelial Carcinoma With Differential Outcomes on Immune Checkpoint Blockade
Authors: Michal Sarfaty, Mahdi Golkaram, Samuel A. Funt, Hikmat Al-Ahmadie, Shannon Kaplan, Fan Song, Ashley Regazzi, Vladimir Makarov, Fengshen Kuo, Irina Ostrovnaya, Venkatraman Seshan, Chen Zhao, Benjamin Greenbaum, Li Liu, Jonathan E. Rosenberg, Timothy A. Chan
Journal: Journal of Clinical Oncology (2023)

Immune checkpoint blockade (ICB) therapy has significantly improved clinical outcomes in bladder cancer. Identification of correlates of benefit is critical to select appropriate therapy for individual patients.
Partial Response Upon Peptide Receptor Radionuclide Therapy in a Highly Proliferative Pancreatic Neuroendocrine Tumor
Authors: Alexander Weich, Sebastian E. Serfling, Steven P. Rowe, Lilja B. Solnes, Andreas K. Buck, Takahiro Higuchi, Rudolf A. Werner
Journal: Clinical Nuclear Medicine (2023)

We report on a patient diagnosed with an aggressive pancreatic neuroendocrine tumor (NET G3; Ki67 = 60%), who underwent pancreatic resection with partial removal of liver lesions. The patient refused chemotherapy. Dual-tracer imaging with 18 F-FDG and somatostatin receptor (SSTR)-targeted PET/CT was conducted. Radiotracer accumulation on both imaging modalities in bilobar hepatic lesions was observed. "Cold" somatostatin analogues with four cycles of peptide receptor radionuclide therapy (PRRT) were initiated, leading to partial response. Even in highly proliferative but differentiated G3 NET (Ki67>55%), SSTR expression in sites of disease should be evaluated, which may then allow PRRT, even as first-line systemic treatment.
Reply to Spek and Duitman
Authors: Justin M. Oldham, Richard J. Allen, Jose M. Lorenzo-Salazar, Carlos Flores, Louise V. Wain, Imre Noth
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Reply to: PCSK6: The endogenous PAR-1 agonist driving pulmonary fibrosis?." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Jejunal Cavernous Hemangioma Mimicking Malignancy With Increased Activity on 18F-FDG PET/CT
Authors: Wen-Shan Huang, Yang-Lin He, Jie Liang, Yu-Lin Su, Jie-Hua Xu
Journal: Clinical Nuclear Medicine (2023)

A 50-year-old woman underwent 18 F-FDG PET/CT to evaluate possible abdominal malignancy, which was revealed by CT. The images showed a large cystic-solid lesion with peripherally increased FDG activity in the left mid-abdomen. Histopathology of the excised lesion confirmed a jejunal cavernous hemangioma. We reported a rare case of jejunal cavernous hemangioma with FDG accumulation on PET/CT, mimicking malignancy.
PCSK6: The Endogenous PAR-1 Agonist Driving Pulmonary Fibrosis?
Authors: C. Arnold Spek, JanWillem Duitman
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"PCSK6: The Endogenous PAR-1 Agonist Driving Pulmonary Fibrosis?." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
FDG PET/CT Imaging of Severe Polymyalgia Rheumatica
Authors: Jeffrey Chen, Veronica Chi Ken Wong, Chuong Bui, Robert Mansberg
Journal: Clinical Nuclear Medicine (2023)

Abstract A 68-year-old woman was referred for an 18 F-FDG PET/CT for evaluation of arthralgia and raised inflammatory markers, which demonstrated intense FDG activity (SUV max , 25.5) at numerous periarticular and extra-articular sites including the cervical and lumbar interspinous bursae, lumbar facet joints, bilateral ischial tuberosities, and greater trochanters and the aorta consistent with active polymyalgia rheumatica.
Chest Wall Keloids Depicted by 18F-Piflufolastat PET/CT Imaging
Authors: Amanda Nguyen, Felipe Martinez, Ba D. Nguyen
Journal: Clinical Nuclear Medicine (2023)

Keloids are pathological scars from exuberant fibroproliferative collagen response and excessive extracellular matrix production usually extending beyond the original wound margins. Although keloids are mostly of dermatological concern, they could be incidentally depicted on scintigraphic planar and PET/CT imaging and could mimic other types of skin diseases. The authors present a case of chest wall keloids documented on 18 F-piflufolastat PET/CT during the evaluation of prostate cancer recurrence.
Adverse event reporting to US Food and Drug Administration and risk evaluation and mitigation strategies
Authors: Deborah L. Thompson, Kerry Welsh, Meghna Alimchandani
Journal: Molecular Therapy (2023)

We are writing in response to an editorial by Byrne et al. entitled "Secondary hemophagocytic lymphohistiocytosis following Zolgensma therapy: An evolving story on the innate response to systemic gene therapy"1 to clarify the process for adverse event reporting to the US Food and Drug Administration (FDA) and the purpose of a Risk Evaluation and Mitigation Strategy (REMS).
Cation/proton antiporters: novel structure-driven pharmaceutical opportunities
Authors: Gal Masrati, Amit Kessel, Nir Ben-Tal
Journal: Trends in Pharmacological Sciences (2023)

Cation/proton antiporters (CPAs) regulate cells' salt concentration and pH. Their malfunction is associated with a range of human pathologies, yet only a handful of CPA-targeting therapeutics are presently in clinical development. Here, we discuss how recently published mammalian protein structures and emerging computational technologies may help to bridge this gap.
Chlordecone (Kepone) poisoning in the French Territories in the Americas
Authors: Dabor Resiere, Jonathan Florentin, Hatem Kallel, Rishika Banydeen, Ruddy Valentino, Moustapha Dramé, José-Louis Barnay, Papa Gueye, Bruno Mégarbane, Hossein Mehdaoui, Rémi Neviere
Journal: The Lancet (2023)
Immunogenicity, safety, and tolerability of a recombinant measles-vectored Lassa fever vaccine: a randomised, placebo-controlled, first-in-human trial
Authors: Roland Tschismarov, Pierre Van Damme, Clara Germain, Ilse De Coster, Mathieu Mateo, Stephanie Reynard, Alexandra Journeaux, Yvonne Tomberger, Kanchanamala Withanage, Denise Haslwanter, Katherine Terler, Sabrina Schrauf, Matthias Müllner, Erich Tauber, Katrin Ramsauer, Sylvain Baize
Journal: The Lancet (2023)
Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial
Authors: Rohit Loomba, Manal F Abdelmalek, Matthew J Armstrong, Maximilian Jara, Mette Skalshøi Kjær, Niels Krarup, Eric Lawitz, Vlad Ratziu, Arun J Sanyal, Jörn M Schattenberg, Philip N Newsome
Journal: The Lancet. Gastroenterology & hepatology (2023)
Regulatory effect of orexin system on various diseases through mTOR signaling pathway
Authors: Ying Song, Beibei Wang, Wenjun Wang, Qiwen Shi
Journal: Trends in Endocrinology and Metabolism (2023)

Orexin (OX)A and OXB are a pair of neuropeptides secreted by orexin-producing neurons in the lateral hypothalamus. The orexin system can regulate many physiological processes through these two receptor pathways, such as feeding behavior, sleep/wake state, energy homeostasis, reward, and the coordination of emotion. Mammalian target of rapamycin (mTOR) can coordinate upstream signals with downstream effectors, thereby regulating fundamental cellular processes and also plays an essential role in the signaling network downstream of the orexin system. In turn, the orexin system can activate mTOR. Here, we review the association of the orexin system with the mTOR signaling pathway mainly by discussing that drugs in various diseases exert their effects on the orexin system, indirectly affecting the mTOR signaling pathway.
Excess mortality attributed to heat and cold: a health impact assessment study in 854 cities in Europe
Authors: Pierre Masselot, Malcolm Mistry, Jacopo Vanoli, Rochelle Schneider, Tamara Iungman, David Garcia-Leon, Juan-Carlos Ciscar, Luc Feyen, Hans Orru, Aleš Urban, Susanne Breitner, Veronika Huber, Alexandra Schneider, Evangelia Samoli, Massimo Stafoggia, Francesca de’Donato, Shilpa Rao, Ben Armstrong, Mark Nieuwenhuijsen, Ana Maria Vicedo-Cabrera, Antonio Gasparrini, Souzana Achilleos, Jan Kyselý, Ene Indermitte, Jouni J.K. Jaakkola, Niilo Ryti, Mathilde Pascal, Klea Katsouyanni, Antonis Analitis, Patrick Goodman, Ariana Zeka, Paola Michelozzi, Danny Houthuijs, Caroline Ameling, Shilpa Rao, Susana das Neves Pereira da Silva, Joana Madureira, Iulian-Horia Holobaca, Aurelio Tobias, Carmen Íñiguez, Bertil Forsberg, Christofer Åström, Martina S. Ragettli, Antonis Analitis, Klea Katsouyanni, First name Surname, Sofia Zafeiratou, Liliana Vazquez Fernandez, Ana Monteiro, Masna Rai, Siqi Zhang, Kristin Aunan
Journal: The Lancet Planetary Health (2023)
Advances in developing ACE2 derivatives against SARS-CoV-2
Authors: Haoran Zhang, Panjing Lv, Jingrui Jiang, Yahui Liu, Ruixi Yan, Sainan Shu, Bing Hu, Han Xiao, Kun Cai, Shuai Yuan, Yan Li
Journal: The Lancet Microbe (2023)
aMAP Score and Its Combination With Liver Stiffness Measurement Accurately Assess Liver Fibrosis in Chronic Hepatitis B Patients
Authors: Rong Fan, Guanlin Li, Ning Yu, Xiujuan Chang, Tamoore Arshad, Wen-Yue Liu, Yan Chen, Grace Lai-Hung Wong, Yiyue Jiang, Xieer Liang, Yongpeng Chen, Xiao-Zhi Jin, Zheng Dong, Howard Ho-Wai Leung, Xiao-Dong Wang, Zhen Zeng, Terry Cheuk-Fung Yip, Qing Xie, Deming Tan, Shaoli You, Dong Ji, Jun Zhao, Arun J. Sanyal, Jian Sun, Ming-Hua Zheng, Vincent Wai-Sun Wong, Yongping Yang, Jinlin Hou
Journal: Clinical Gastroenterology and Hepatology (2023)
Macrophage STING signaling promotes NK cell to suppress colorectal cancer liver metastasis via 4-1BBL/4-1BB co-stimulation
Authors: Yu Sun, Haoran Hu, Zheng Liu, Jian Xu, Yiyun Gao, Xinyu Zhan, Shun Zhou, Weizhe Zhong, Dongming Wu, Ping Wang, Zhuqing Rao, Lianbao Kong, Haoming Zhou
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background and aims Macrophage innate immune response plays an important role in tumorigenesis. However, the role and mechanism of macrophage STING signaling in modulating tumor microenvironment to suppress tumor growth at secondary sites remains largely unclear. Methods STING expression was assessed in liver samples from patients with colorectal cancer (CRC) liver metastasis. Global or myeloid stimulator of interferon gene (STING)-deficient mice, myeloid NOD-like receptor protein 3 (NLRP3)-deficient mice, and wild-type (WT) mice were subjected to a mouse model of CRC liver metastasis by intrasplenic injection of murine colon carcinoma cells (MC38). Liver non-parenchymal cells including macrophages and natural killer (NK) cells were isolated for flow cytometry analysis. Bone marrow-derived macrophages pretreated with MC38 were co-cultured with splenic NK cells for in vitro studies. Results Significant activation of STING signaling were detected in adjacent and tumor tissues and intrahepatic macrophages. Global or myeloid STING-deficient mice had exacerbated CRC liver metastasis and shorten survival, with decreased intrahepatic infiltration and impaired antitumor function of NK cells. Depletion of NK cells in WT animals increased their metastatic burden, while no significant effects were observed in myeloid STING-deficient mice. STING activation contributed to the secretion of interleukin (IL)-18 and IL-1β by macrophages, which optimized antitumor activity of NK cells by promoting the expression of 4-1BBL in macrophages and 4-1BB in NK cells, respectively. Moreover, MC38 treatment activated macrophage NLRP3 signaling, which was inhibited by STING depletion. Myeloid NLRP3 deficiency increased tumor burden and suppressed activation of NK cells. NLRP3 activation by its agonist effectively suppressed CRC liver metastasis in myeloid SITNG-deficient mice. Conclusions We demonstrated that STING signaling promoted NLRP3-mediated IL-18 and IL-1β production of macrophages to optimize the antitumor function of NK cells via the co-stimulation signaling of 4-1BBL/4-1BB.
Inactivation of interleukin-30 in colon cancer stem cells via CRISPR/Cas9 genome editing inhibits their oncogenicity and improves host survival
Authors: Luigi D'Antonio, Cristiano Fieni, Stefania Livia Ciummo, Simone Vespa, Lavinia Lotti, Carlo Sorrentino, Emma Di Carlo
Journal: Journal for ImmunoTherapy of Cancer (2023)

Progression of colorectal cancer (CRC), a leading cause of cancer-related death worldwide, is driven by colorectal cancer stem cells (CR-CSCs), which are regulated by endogenous and microenvironmental signals. Interleukin (IL)-30 has proven to be crucial for CSC viability and tumor progression. Whether it is involved in CRC tumorigenesis and impacts clinical behavior is unknown.IL30 production and functions, in stem and non-stem CRC cells, were determined by western blot, immunoelectron microscopy, flow cytometry, cell viability and sphere formation assays. CRISPR/Cas9-mediated deletion of the IL30 gene, RNA-Seq and implantation of IL30 gene transfected or deleted CR-CSCs in NSG mice allowed to investigate IL30's role in CRC oncogenesis. Bioinformatics and immunopathology of CRC samples highlighted the clinical implications.We demonstrated that both CR-CSCs and CRC cells express membrane-anchored IL30 that regulates their self-renewal, via WNT5A and RAB33A, and/or proliferation and migration, primarily by upregulating CXCR4 via STAT3, which are suppressed by IL30 gene deletion, along with WNT and RAS pathways. Deletion of IL30 gene downregulates the expression of proteases, such as MMP2 and MMP13, chemokine receptors, mostly CCR7, CCR3 and CXCR4, and growth and inflammatory mediators, including ANGPT2, CXCL10, EPO, IGF1 and EGF. These factors contribute to IL30-driven CR-CSC and CRC cell expansion, which is abrogated by their selective blockade. IL30 gene deleted CR-CSCs displayed reduced tumorigenicity and gave rise to slow-growing and low metastatic tumors in 80% of mice, which survived much longer than controls. Bioinformatics and CIBERSORTx of the 'Colorectal Adenocarcinoma TCGA Nature 2012' collection, and morphometric assessment of IL30 expression in clinical CRC samples revealed that the lack of IL30 in CRC and infiltrating leucocytes correlates with prolonged overall survival.IL30 is a new CRC driver, since its inactivation, which disables oncogenic pathways and multiple autocrine loops, inhibits CR-CSC tumorigenicity and metastatic ability. The development of CRISPR/Cas9-mediated targeting of IL30 could improve the current therapeutic landscape of CRC.
Impact of Early Life Factors on Metabolic Phenotypes of Obesity in Preschool Children
Authors: Zijun Liao, Xianghui Xie, Jing Wang, Yiren Chen, Ting Zhang, Gongshu Liu, Fangfang Chen
Journal: Diabetes Care (2023)

OBJECTIVE To investigate the impact of factors in the first 1,000 days of life on metabolic phenotypes of obesity in preschool children in a cohort study. RESEARCH DESIGN AND METHODS We recruited 3-year-old children for the study. Early life factors included maternal age at delivery, maternal education, prepregnancy BMI, gestational weight gain, gravidity, history of gestational diabetes mellitus, delivery mode, gestational age, family history of metabolic disorders, paternal education, annual family income, child sex, birth weight, and breastfeeding duration. According to BMI and metabolic status, children were classified as metabolically healthy (no metabolic risk factors) with normal weight (MHNW), metabolically unhealthy (one or more metabolic risk factors) with normal weight (MUNW), metabolically healthy with overweight or obesity (MHO), and metabolically unhealthy with overweight or obesity (MUO). RESULTS We recruited 3,822 children for the study, with 3,015 analyzed. Accelerated BMI z score growth rate between 6 and 24 months was associated with MHO (β = 0.022; 95% CI 0.009, 0.036) and MUO (β = 0.037; 95% CI 0.018, 0.056). Maternal overweight (odds ratio [OR] 3.16; 95% CI 1.55, 6.42) and obesity (OR 8.14; 95% CI 3.73, 17.76) before pregnancy and macrosomia (OR 2.47; 95% CI 1.32, 4.59) were associated with MHO, and maternal obesity before pregnancy (OR 6.35; 95% CI 2.17, 18.52) increased the risk of MUO. CONCLUSIONS Early life factors, such as maternal obesity and accelerated BMI growth rate between 6 and 24 months, were related not only to MHO but also to MUO. Children with these early life factors should be given interventions for weight control to prevent metabolic abnormalities.
The infusion of ex vivo, interleukin-15 and -21-activated donor NK cells after haploidentical HCT in high-risk AML and MDS patients—a randomized trial
Authors: Kyoo-Hyung Lee, Suk Ran Yoon, Jeong-Ryeol Gong, Eun-Ji Choi, Hun Sik Kim, Chan-Jeoung Park, Sung-Cheol Yun, Soo-Yeon Park, Sol-Ji Jung, Hanna Kim, Soo Yun Lee, Haiyoung Jung, Jae-Eun Byun, Mirang Kim, Seon-Young Kim, Jeong-Hwan Kim, Je-Hwan Lee, Jung-Hee Lee, Yunsuk Choi, Han-Seung Park, Young-Shin Lee, Young-Ah Kang, Mijin Jeon, Jimin Woo, Hyeran Kang, Seunghyun Baek, Su Mi Kim, Hoon-Min Kim, Kwang-Hyun Cho, Inpyo Choi
Journal: Leukemia (2023)
EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update
Authors: Bernhard Hellmich, Beatriz Sanchez-Alamo, Jan H Schirmer, Alvise Berti, Daniel Blockmans, Maria C Cid, Julia U Holle, Nicole Hollinger, Omer Karadag, Andreas Kronbichler, Mark A Little, Raashid A Luqmani, Alfred Mahr, Peter A Merkel, Aladdin J Mohammad, Sara Monti, Chetan B Mukhtyar, Jacek Musial, Fiona Price-Kuehne, Mårten Segelmark, Y K Onno Teng, Benjamin Terrier, Gunnar Tomasson, Augusto Vaglio, Dimitrios Vassilopoulos, Peter Verhoeven, David Jayne
Journal: Annals of the Rheumatic Diseases (2023)

Background Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. Methods Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations. Results Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4–5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV. Conclusions In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.
Inhibition of KDM7A/B histone demethylases restores H3K79 methylation and protects against osteoarthritis
Authors: Reem Assi, Chahrazad Cherifi, Frederique M.F. Cornelis, Qiongfei Zhou, Lies Storms, Sofia Pazmino, Rodrigo Coutinho de Almeida, Ingrid Meulenbelt, Rik J. Lories, Silvia Monteagudo
Journal: Annals of the Rheumatic Diseases (2023)

Objectives In osteoarthritis, methylation of lysine 79 on histone H3 (H3K79me), a protective epigenetic mechanism, is reduced. Histone methylation levels are dynamically regulated by histone methyltransferases and demethylases. Here, we aimed to identify which histone demethylases regulate H3K79me in cartilage and investigate whether their targeting protects against osteoarthritis. Methods We determined histone demethylase expression in human non-osteoarthritis and osteoarthritis cartilage using qPCR. The role of histone demethylase families and subfamilies on H3K79me was interrogated by treatment of human C28/I2 chondrocytes with pharmacological inhibitors, followed by western blot and immunofluorescence. We performed C28/I2 micromasses to evaluate effects on glycosaminoglycans by Alcian blue staining. Changes in H3K79me after destabilisation of the medial meniscus (DMM) in mice were determined by immunohistochemistry. Daminozide, a KDM2/7 subfamily inhibitor, was intra-articularly injected in mice upon DMM. Histone demethylases targeted by daminozide were individually silenced in chondrocytes to dissect their role on H3K79me and osteoarthritis. Results We documented the expression signature of histone demethylases in human non-osteoarthritis and osteoarthritis articular cartilage. Inhibition of Jumonji-C demethylase family increased H3K79me in human chondrocytes. Blockade of KDM2/7 histone demethylases with daminozide increased H3K79me and glycosaminoglycans. In mouse articular cartilage, H3K79me decayed rapidly upon induction of joint injury. Early and sustained intra-articular treatment with daminozide enhanced H3K79me and exerted protective effects in mice upon DMM. Individual silencing of KDM7A/B demethylases in human chondrocytes demonstrated that KDM7A/B mediate protective effects of daminozide on H3K79me and osteoarthritis. Conclusion Targeting KDM7A/B histone demethylases could be an attractive strategy to protect joints against osteoarthritis.